Mg Woldring

Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET)

To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-11C)-tyrosine by 11C-carboxylation of the appropriate α-lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-11C)-Tyrosine in 0.1 N NaH2PO4 buffer was prepared with a radiochemical yield of 8%–16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-11C)-tyrosine in physiological saline was obtained in 2%–4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-11C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma.

Rapid synthesis and purification of carbon-11 labelled DOPA: a potential agent for brain studies

A rapid methods for preparation and purification of β-(3,4-dihydroxyphenyl)-D,L-α-alanine-1-11C (11C-DOPA), using 11CO2 as the radioactive precursor is described. Carboxylation of an α-lithioisocyanide, containing protected hydroxylic groups, was followed by a three-step hydrollsis of the intermediate α-isocyano carboxylic acid. Preliminary experiments in rats indicate that the compound is preferentially decarboxylated in brain areas rich in dopamine containing neurons.

Excitation functions for the production of bromine-75: A potential nuclide for the labelling of radiopharmaceuticals

Abstract Based on a theoretical evaluation of the charged particle induced reactions leading to 75 Br the four most promising reactions, 76 Se (p,2n) 75 Br , 76 Se (d,3n) 75 Br , 75 As ( 3 He ,3n) 75 br and 75 As ( 4 He ,4n) 75 Br , were selected for excitation function measurements. From the measured excitation functions the production rates and radionuclide purities were calculated. The proton induced reaction on 76 Se showed the highest production rate (118 mCi/μAh) while the contamination of the undesired nuclide 76 Br is limited to 1.4%.

C-11 LABELED METHYLLITHIUM AS METHYL DONATING AGENT - THE ADDITION TO 17-KETO STEROIDS

Abstract Carbon-11 labelled methyllithium was prepared from 11 C-methyl-iodide by halogen-metal interconversion with n-butyllithium. Within 10 min the exchange was nearly quantitative. The methyl donating properties of this high specific active 11 C-precursor were demonstrated by the addition to 17-keto steroids. 11 C-labelled 17α-methylestradiol, 17α-methyltestosterone and 17α-methylestradiol 3-methylether with specific activities of 1−5 Ci/mmol were prepared.

Preparation of carbon-11 labelled phenylalanine and phenylglycine by a new amino acid synthesis☆

Of the cyclotron-produced short-lived isotopes carbon-11 (t12 = 20.4 min; β+) is one of the most promising as label for radiopharmaceuticals. To prepare 11C-labelled amino acids for evaluation as pancreas scanning agents a new rapid amino acid synthesis was developed. The method is based on the carboxylation of α-lithioisocyanides with 11CO2, followed by hydrolysis of the intermediate reaction product to the desired amino acid. By this method DL-α-phenylalanine-1-11C and DL-α-phenylglycine-1-11C were prepared. The precursor 11CO2 was produced via the 14N(p, α)11C reaction by bombardment of a flow of nitrogen gas mixed with 0.1% O2 with 20 MeV protons. The target system is described.

Synthesis of DL-[1-11C]methionine.

dl-[1-11C]methionine has been synthesized by carboxylation of the corresponding α-lithioisocyanide with a radiochemical yield of 8–14% (EOS, 35 min).

Synthesis of no-carrier-added L- and D-[1-11C]-DOPA.

No-carrier-added DL-[1-11C]-DOPA has been synthesized by carboxylation of an alpha-lithioisocyanide with a radiochemical yield of up to 15% without correction for decay. The total synthesis time is 30 min. The resolution of the D- and L-isomers was accomplished within 16 min by HPLC using a chiral stationary phase and a phosphate buffer of pH 4.5 as eluent.

Fast recovery by dry distillation of 75Br induced in reusable metal selenide targets via the 76Se(p,2n)75Br reaction

Abstract A number of metal selenides were investigated as target material for the production of 75Br by the 76Se(p,2n)75Br reaction. Ag2Se, CuAgSe, and Cu2Se met the rqquirements for an economical and fast production procedure. These selenides were found to be stable during bombardment with 1–4 μA 28 MeV protons (beam dimension 0.4 cm2) and at the dry distillation temperature of 1473 K. A target system was developed for radiobromine production with a 7 μA 28−22 MeV proton beam on Cu2Se. At EOB the calculated thick target yield is 1.59 GBq/μAh (43 mCi/μAh) and the radionuclidic purity is 98.6%. The radiobromine was separated from Cu2Se by dry distillation at 1473 K and collected for 80–95% on platinum wool pretreated with CaCl2. Radiochemical analysis showed the radiobromine to be Br− for 95% and BrO3− for 5%. The total loss of selenide after irradiation and distillation was found to be less than 0.1%.

Syntheses of carbon-11 labelled ornithine and lysine. Preliminary accumulation studies in rats with Walker 256 carcinosarcoma

DL-[1-11C]ornithine and lysine have been synthesized by carboxylation of the corresponding alpha-lithioisocyanide with a radiochemical yield of up to 14% without correction for decay. The total preparation time is 50 min. Accumulation of both DL-[1-11C]ornithine and lysine in Walker 256 carcinosarcoma is observed, with a tumor/non-tumor ratio of 4.9 and 4.5 respectively, at 45 min after intravenous injection.

Determination of the functional residual capacity during exercise

A rebreathing technique is described for measuring FRC during exercise. Good agreement was found between this technique and a standard helium dilution method using a water spirometer at rest. Measurements of FRC in ten volunteers showed a significant decrease of FRC at the onset of progressive exercise. The FRC remained significantly smaller than the resting value up to loads of 150 W.